A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
CLEVER-1 targeting antibody, bexmarilimab, supports HLA-DR expression and alters ex vivo responsiveness to azacitidine and venetoclax in myeloid malignancies
Tekijät: Aakko, Sofia; Ylitalo, Arno; Kuusanmäki, Heikki; Rannikko, Jenna H.; Björkman, Mari; Mandelin, Jami; Heckman, Caroline A.; Kontro, Mika; Hollmén, Maija
Kustantaja: Springer Science and Business Media LLC
Kustannuspaikka: BERLIN
Julkaisuvuosi: 2025
Journal: Scientific Reports
Tietokannassa oleva lehden nimi: Scientific Reports
Lehden akronyymi: SCI REP-UK
Artikkelin numero: 16775
Vuosikerta: 15
Numero: 1
Sivujen määrä: 13
ISSN: 2045-2322
eISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-025-01675-y
Verkko-osoite: https://doi.org/10.1038/s41598-025-01675-y
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/498613459
Treatment of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) requires new therapy options, especially for patients uneligible for intense chemotherapy or with relapsed or refractory disease. CLEVER-1 is a myeloid checkpoint protein, which can be targeted with a therapeutic function blocking antibody, bexmarilimab. Bexmarilimab has shown clinical efficacy in different solid tumors. Here, we show preclinical data demonstrating expression of CLEVER-1 on immature malignant myeloid cells and their derivates in MDS and AML bone marrow samples and AML cell lines. Highest CLEVER-1 levels were observed in AML with monocytic differentiation. Ex vivo treatment of AML/MDS bone marrow samples with bexmarilimab led to an increase in antigen-presenting human leukocyte antigen DR isotype (HLA-DR) molecule expression. Combination of bexmarilimab with current standard-of-care (SoC) drugs, azacitidine and venetoclax, showed potential for HLA-DR induction and enhanced killing of leukemic cells, respectively. Our non-clinical findings support the feasibility of CLEVER-1 inhibition in AML/MDS to induce antigen presentating molecule expression and potentially, an anti-leukemic effect together with SoC. Therapeutic targeting of CLEVER-1 with bexmarilimab is currently undergoing clinical investigation in the BEXMAB trial (NCT05428969).
Ladattava julkaisu This is an electronic reprint of the original article. |  |
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This study was supported by Post Docs in Companies grant from the Finnish Cultural Foundation to SA, Business Finland funding 8040/31/2019 (Cancer IO) to Faron Pharmaceuticals, Finnish Medical Foundation and Cancer Foundation Finland to MK, and Academy of Finland fellowship funding and Sigrid Jusélius grant to MH. The FIMM High Throughput Biomedicine Unit is financially supported by the University of Helsinki (HiLIFE) and Biocenter Finland.
